FDA Accepts Shire's SHP555 NDA for Chronic Idiopathic Constipation

If approved, prucalopride will be the only readily available 5-HT4 agonist in the US for CIC in adults.

The US Food and Drug Administration (FDA) accepted the submission of a new drug application (NDA) for SHP555 (prucalopride) as a potential once-daily treatment option for chronic idiopathic constipation (CIC) in adults, announced Shire.

The designated prescription drug user fee act (PDUFA) action date is set to occur on or around Dec. 21, 2018.

“Chronic idiopathic constipation is a commonly-occurring condition that affects nearly 1 in 8 people in the US,” William Chey, MD, professor of gastroenterology and nutrition sciences, director, GI Nutrition and Behavioral Wellness Program, University of Michigan Health System, said in a statement. “Many patients use over-the-counter and prescription medicines, including laxatives, but continue to have constipation symptoms.”

Prucalopride, a high affinity, selective serotonin type 4 receptor agonist, is a gastrointestinal prokinetic agent that simulates colonic peristalsis which increases bowel motility.

The NDA submission is based off study data from 5 main phase 3 and 1 phase 4 double-blind, placebo-controlled clinical trials. Prucalopride has also been studied in more than 90 clinical trials over the last 20 years.

The 6 trials evaluated the efficacy and safety of prucalopride 2 mg daily in those with CIC. Overall, there were 2484 adult patients in the integrated efficacy analysis and 2552 adult patients included in the integrated safety analysis.

Study findings concluded that significantly more patients treated with prucalopride versus placebo (27.8% vs. 13.2%, respectively) achieved an average of 3 or more spontaneous, complete bowel movements per week throughout the 12-week treatment period.

Common treatment-emergent adverse effects in the prucalopride group, greater than or equal to 5%, were gastrointestinal disorders (nausea, diarrhea and abdominal pain) and headache. The proportion of those who experienced adverse cardiovascular effects were comparable between groups (2% for prucalopride vs. 1.8% for placebo).

Serious treatment-emergent adverse effects were reported in 1.6% of patients who received prucalopride vs. 2.4% who received placebo.

An observational, pharmacoepidemiology safety study was conducted to estimate, in real-world settings, the risk of major adverse cardiovascular events in those treated with

prucalopride vs. patients treated with polyethylene glycol. Drugs similar to prucalopride have been associated with cardiovascular effects in the past.

Prucalopride is currently an investigational product and not approved for us in the US by the FDA. It is however, currently approved, available and marketed in the European Union as Resolor and indicated for symptomatic treatment of chronic constipation in adults where laxatives fail to provide adequate relief.

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